A QUANTUM
MECHANICAL
APPROACH TO
UNDERSTANDING
DNA MUTATIONS
F rom the unfortunate passing of can-
cer patient Henrietta Lacks came
the discovery that the cells from her cervi-
cal tumor were extremely robust and could
be easily kept alive in culture. These cells,
known as HeLa cells, have helped scientists
test cancer treatments, formulate various
vaccines, create imaging techniques, and
much more, but also have brought about
pressing questions.1,2 Despite frequent ge-
netic mutations that would cause ordinary
cell lines to quickly die, how are some HeLa
cells mutation-free? What triggers muta-
tions in cells, and more importantly, can
such mutations be prevented? The key to
answering these questions lies in under-
standing DNA, the code for life, a pattern of
nucleotides unique to every living creature
that results in the broad diversity of traits
we see in life today. Changing even a single
nucleotide in an organism’s code could shift
a cell’s fate onto an unfortunate path, or
give an organism a useful trait. Since DNA’s
discovery in the late 1860s, the reasons
for why and how DNA evolves over time
were thought to be the key to linking the
macroscopic observation of evolution with
molecular and cell biology. Starting in the
mid-1900s, Per-Olov Löwdin, often hailed
as a founding father of quantum chemistry,
began to offer a quantum mechanical ap-
proach to some of the mysteries behind ge-
netic mutations, helping to inspire the field
of quantum biology and breakthroughs in
DNA research that brings us closer than
ever to solving the mysteries of DNA mu-
tations and manipulating the genetic code.
WHAT IS QUANTUM
TUNNELING?
Although several scientists in the ear-
ly 1900s like Albert Einstein, Max Planck,
and Erwin Shrödinger had formally re-
written the laws of physics to explain the
wave-particle behavior of small-scale sys-
tems and subatomic particles, microbiolo-
gy and biochemistry had not advanced far
enough to truly understand how these con-
cepts applied to biological systems. Such
an understanding wasn’t prominent until
the mid-1900s, when Löwdin and other
FALL 2019 | Berkeley Scientific Journal
BY MICHELLE YANG
scientists started applying these concepts
to chemical and biological systems. Löw-
din specifically employed the concept of
quantum tunneling, which explains how
the wave-like properties of small particles
allow them to pass through higher energy
barriers that classically would block normal
objects.2
In both classical and quantum sys-
tems, an object’s position and momentum
are governed by its surroundings, more
precisely named “potential” in quantum
settings. Classically, during a roller coaster
ride, a cart goes faster when going downhill
and slower when going uphill. By the law of
energy conservation, if a cart does not have
enough kinetic energy to overcome the po-
tential energy “hill” created by a tall stretch
of track, it will roll back down. In quantum
systems, however, the wave-like properties
of subatomic particles mean that protons
behave in ways not explained by classical
physics. Unlike a roller coaster cart, which
has a clearly known position and momen-
tum at any given moment, protons are
basically waves with mass, meaning they
37
Figure 1: Model for hydrogen bonding. A proton inside a hydrogen bond (modeled by the
wave function) is bounded by an asymmetric double well potential. Initially it sits in the low-
est well, but after some time, the probability of the proton going through the barrier increas-
es, and the proton will transfer to the other side. When this transfer happens, bonds between
atoms can change, shown by the diagram above each graph.

have no exact position or momentum. Due
to their wave-like properties, protons can
“tunnel” through certain steep hills or high
potential barriers that would otherwise
prevent a classical particle from moving
past.3,4 Higher and wider potential barri-
ers (i.e a higher activation energy for pro-
ton events to occur) are more difficult for
protons to bypass, and thus the timing and
probability of a tunneling event depend on
the barrier, the energy of the particle, and
outside perturbations that could affect the
system.3,4,5,6
A particularly useful application of
particle tunneling theory is in hydrogen
bonding, where a proton sits inside a po-
tential well (Fig. 1).5,6 Due to the unique
structures of DNA nucleotides, favorable
“Due to their wave-
like properties, protons
can ‘tunnel’ through
certain steep hills or
high potential barriers
that would otherwise
prevent a classical
particle from moving
past.”
hydrogen bonding only occurs between
complementary base pairs, just like how
distinctly shaped puzzle pieces only fit
with matching pieces. Adenosine nucleo-
tides will only bind to thymine nucleotides,
while cytosines will only bind to guanines.
LÖWDIN’S HYPOTHESIS:
PROTON TUNNELING IS
A POSSIBLE REASON
FOR CHANGES IN THE
GENETIC CODE
By combining the role of
hydrogen bonding in DNA with
the quantum mechanical view of
hydrogen bonding, Löwdin sug-
gested a chemical mechanism and
quantitative approach to estimate
how and how often a spontaneous mu-
tation in DNA could occur.4,5 When a pro-
ton involved in hydrogen bonding between
two nucleotides undergoes tunneling,
the event triggers another proton
tunneling event in the reverse di-
rection, modifying the shape
of both nucleotides. If this
change is permanent, then
during replication, the two
altered nucleotides bind
to mismatched pairs, intro-
ducing a permanent change to
the genetic code (Fig. 2). Löwdin
went even further to propose that as

38 Berkeley Scientific Journal | FALL 2019

 a consequence of time evo- scientists more information on how the
lution, these tunneling pattern of base pairs and location within a
events happen more chromosome affects the likelihood of ge- “Current calculations
and more frequently as netic mutation.7,8 estimate 1 in a billion to
we age, meaning spon- Luckily, the potential barrier for a
taneous mutations are proton to tunnel through is high and wide a trillion base pairs
more likely to occur, af- enough such that spontaneous mutation ever spontaneously
fecting our body’s health without changes in the chemical environ-
and ability to function.4,5 ment is a rare occurrence; current calcula- change.”
tions estimate one in a billion to a trillion
MODERN base pairs ever spontaneously changes.9,10
Still, the accumulation of proton tunneling proton to a higher energy level, lowering
TECHNIQUES AND
events throughout our lifetimes represents the potential barrier, or perturbing the sur-
A PROMISING FUTURE changes to our genetic code, which more roundings in some other fashion. Critical-
often than not, are harmful rather than ly, these mutations may ultimately trigger
Using calculations based helpful. The risk for cancer increases as cancerous cell growth.5 While the myster-
on quantum mechan- humans age, and could serve as further ev- ies behind the code that governs almost
ics behind these idence for Löwdin’s belief that proton tun- all lifeforms may seem unending, perhaps
proton shifts, re- neling events increase as time progresses.4,5 there will be a day when our understanding
searchers now are Furthermore, outside forces like radiation, of genetic mutations based on the fields of
mapping out mu- exposure to UV light, and other chemicals quantum and computational biology will
tation “hot spots,” can increase the chance for a proton tun- allow us to fully understand and even ma-
locations in DNA neling event to occur, either by exciting the nipulate mutation-causing mechanisms.
more susceptible
to proton tunnel-
ing. By plotting
these hot spots
on a mutation
spectrum, scientists
can determine how
DNA hot spots are
distributed and
investigate what
differentiates these
locations from other
parts of the genome.8
To generate this data,
researchers calculated
the potential barrier for each
pairing, which requires information
on how the arrangement of base pairs af-
fect the height and width of such a barrier.
Locations with low potential barriers of-
ten mark these mutation hot spots, giving

Figure 2: Molecular diagram for proton transfers and impact on replication. Starting from the top left, normal T-A nucleo-
base pairing is shown. After a proton tunneling event (on T nitrogen to A nitrogen), another proton transfer is triggered
(from top nitrogen of A to T*), resulting in two changed nucleobase structures that have different complementary base
pairing than before. After replication, T* binds to G, and A* binds to C, permanently altering the genetic code. Right side
shows proton tunneling mechanism for C-G pairing.

FALL 2019 | Berkeley Scientific Journal 39

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1. Deerink, T. (2017). Retrieved from
https://www.flickr.com/photos/nih-
gov/34948768633
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